BACKGROUND The most critical issue to organ transplantation is the identification of new sources of organs. The present manuscript illustrates the state-of-the-art regenerative medicine (RM) investigations aiming to manufacturing abdominal organs for transplant purposes. METHODS This manuscript focuses on research in the bioengineering and regeneration of kidneys, insulin-producing cells, livers and small bowel. The main technology currently under development exploits the seeding of cells on supporting scaffolding material. Despite favorable preliminary results obtained with relatively simple, hollow organs, when more complex organs are considered, the scenario changes dramatically. Investigations are still in early stages, and clinical translation is not yet foreseeable based on current knowledge and information. Obstacles are numerous but we believe the critical factor hampering success is lack of in-depth understanding of the extracellular matrix (ECM) and cell-ECM interactions, as well as the mechanisms with which organs develop in utero. CONCLUSIONS The success of RM to generate transplantable abdominal organs relies heavily on progress in (stem) cell therapies, developmental and ECM biology, and in the thorough understanding of the intricate relationship and interplay between cells and the ECM. This will require enormous investments in financial and medical resources, which ideally should be embarked upon by governments, the private sector and academia.